Determination of pharmacological inhibition of ALDH2 by ethanol clearance in mice.

OBJECTIVES: Retinoic acid plays diverse physiological and pathophysiological roles in reproduction, immune function, energy metabolism and carcinogenesis. Because of the potential benefits of inhibiting retinoic acid biosynthesis in certain disease states, efforts are underway to develop inhibitors of retinoic acid biosynthesis via inhibition of the aldehyde dehydrogenase-1 A (ALDH1A) family of enzymes. However, many potential ALDH1A inhibitors also inhibit the related ALDH2 enzyme that plays a role in the metabolism of ethanol. Accurate in vitro assessment of ALDH2 inhibition is problematic, and to date, there are no published in vivo assays to determine inhibition of ALDH2 by candidate ALDH1A inhibitors. STUDY DESIGN: To address this, we developed a novel gas-chromatography-mass-spectrometry ethanol clearance assay in mice using orally administered ethanol and serial measurement of ethanol over time. We then used this assay to determine pharmacological inhibition of ALDH2 by candidate ALDH1A inhibitors. RESULTS: Ethanol clearance in untreated male mice occurs within sixty minutes. Male mice treated with WIN 18,446, a known ALDH1A inhibitor that also inhibits ALDH2, demonstrated significant inhibition of ethanol clearance compared to untreated controls. Novel pyrazole and piperazine ALDH1A inhibitors were then tested with the piperazine inhibitor demonstrating ALDH2 inhibition via impaired ethanol clearance while the pyrazole inhibitor did not interfere with ethanol metabolism, suggesting a lack of ALDH2 inhibition. CONCLUSIONS: Inhibition of ethanol clearance is a useful in vivo method of inferring pharmacologic inhibition of hepatic ALDH2. This assay may be useful in the development of novel ALDH1A specific inhibitors for a variety of therapeutic indications.

Chalazion-mimicked eyelid angiosarcoma in a young Asian with good prognosis: a case report.

BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.

Dietary Vitamin A Affects the Function of Incretin-Producing Enteroendocrine Cells in Male Mice Fed a High-Fat Diet.

BACKGROUND: Retinol-binding protein 2 (RBP2) is an intracellular carrier for vitamin A in the absorptive enterocytes. Mice lacking RBP2 (Rbp2-/-) display an unexpected phenotype of obesity, glucose intolerance, and elevated glucose-dependent insulinotropic polypeptide (GIP) levels. GIP and glucagon-like peptide 1 (GLP-1) are incretin hormones secreted by enteroendocrine cells (EECs). We recently demonstrated the presence of RBP2 and other retinoid-related proteins in EECs. OBJECTIVES: Given RBP2's role in intracellular retinoid trafficking, we aimed to evaluate whether dietary vitamin A affects incretin-secreting cell function and gene expression. METHODS: Male Rbp2-/- mice and sex- and age-matched controls (n = 6-9) were fed a high-fat diet (HFD) for 18 wk containing normal (VAN, 4000 IU/kg of diet) or low (VAL, 25% of normal) vitamin A concentrations. Body weight was recorded biweekly. Plasma GIP and GLP-1 levels were obtained fasting and 30 min after an oral fat gavage at week 16. Glucose tolerance tests were also performed. Mice were killed at week 18, and blood and tissue samples were obtained. RESULTS: Rbp2-/- mice displayed greater weight gain on the VAN compared with the VAL diet from week 7 of the intervention (P ≤ 0.01). Stimulated GIP levels were elevated in Rbp2-/- mice compared with their controls fed the VAN diet (P = 0.02), whereas their GIP response was lower when fed the VAL diet (P = 0.03). Although no differences in GLP-1 levels were observed in the VAN diet group, a lower GLP-1 response was seen in Rbp2-/- mice fed the VAL diet (P = 0.02). Changes in incretin gene expression and that of other genes associated with EEC lineage and function were consistent with these observations. Circulating and hepatic retinoid levels revealed no systemic vitamin A deficiency across dietary groups. CONCLUSIONS: Our data support a role for RBP2 and dietary vitamin A in incretin secretion and gene expression in mice fed a HFD.

CFTR dysregulation drives active selection of the gut microbiome.

Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not clear. To test the relationships between CFTR dysfunction, microbes, and intestinal health, we established a germ-free (GF) CF mouse model and demonstrated that CFTR gene mutations are sufficient to alter the GI microbiome. Furthermore, flow cytometric analysis demonstrated that colonized CF mice have increased mesenteric lymph node and spleen TH17+ cells compared with non-CF mice, suggesting that CFTR defects alter adaptive immune responses. Our findings demonstrate that CFTR mutations modulate both the host adaptive immune response and the intestinal microbiome.

Clinical Features and Outcomes of Patients with Orbital Schwannoma.

PURPOSE: To report the clinical features, treatment, and outcome of 11 patients with orbital schwannoma in Korean patients. METHODS: The medical records of 11 orbital schwannoma patients treated between April 2007 and April 2021 were retrospectively reviewed. The demographic data, clinical characteristics, radiological features, and outcomes were reviewed. RESULTS: The mean age at the time of diagnosis was 49.00 ± 14.45 years. The most common initial symptom was ocular protrusion (n = 7), and other symptoms were decreased visual acuity ( n = 5), restriction of eye movement ( n = 4), swelling ( n = 3), and pain ( n = 2). Locations of tumors were superomedial; followed by the orbital apex and inferolateral. The most common shape seen in our patients was beads like multilobulated appearance; followed by a round, oval, fusiform, and dumbbell shape. MRI of T1-weighted revealed isointense or hypointense, whereas the T2-weighted indicated hyper or isointense lesion. Five patients had optic neuropathy at presentation, and 1 of them showed improved vision after surgery. Complete or incomplete excision was performed for all. Surgical complications include decreased vision and paraesthesia. There has been no recurrence to date. CONCLUSIONS: Orbital schwannoma is a rare disease and it is difficult to distinguish it from other orbital tumors because the initial symptoms are nonspecific. Differential diagnosis by combining the shape, location, and contrast enhancement findings seen on computed tomography and magnetic resonance imaging can be helpful in surgical treatment. Complete excision gives the best results without recurrence, but if the patient is in an inaccessible location, only surgery to reduce the volume can satisfy the patient without recurrence.

Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

BACKGROUND: Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility. METHODS: A series of piperazine compounds that inhibited ALDH1A1 were identified and their inhibitory activity was characterized in vitro using purified recombinant enzymes and cell-based assay systems. One potent compound, FSI-TN42 (N42) was examined for its oral bioavailability and pharmacodynamic effects. In addition, its effect on weight gain was investigated by daily oral administration to C57BL/6 male mice receiving a HFD, and compared with mice receiving WIN18446 or vehicle alone (n = 6/group, 200 mg compound/kg body weight) for 5 weeks. Body weights were measured weekly, and a glucose tolerance test was performed after 4 weeks of treatment. Tissues were collected to determine changes in adipose weight, hepatic lipidosis, retinoid metabolism, and expression of genes associated with RA and lipid metabolism. RESULTS: N42 irreversibly binds and inhibits ALDH1A1 in vitro with a low nM IC50 and 800-fold specificity for ALDH1A1 compared to ALDH1A2. Daily oral administration of N42 significantly suppressed weight gain (P < 0.05) and reduced visceral adiposity (p < 0.05) in mice fed a HFD without the hepatic lipidosis observed with WIN18446 treatment. CONCLUSIONS: We developed a potent and specific inhibitor of ALDH1A1 that suppressed weight gain in mice fed a HFD. These findings demonstrate that inhibition of ALDH1A1 is a feasible target for drug development to treat and/or prevent obesity.

Blepharoptosis among Korean adults: age-related prevalence and threshold age for evaluation.

BACKGROUND: To evaluate the prevalence of blepharoptosis among Korean adults and the characteristics of blepharoptosis patients, and to determine an appropriate age threshold for recommending blepharoptosis evaluation. METHODS: The Korean National Health and Nutrition Examination Survey (KNHANES-V) was conducted in 2010-2012. We extracted data on 17,878 Korean adults aged more than and equal to 19 years included in KNHANES-V, and determined blepharoptosis prevalence according to age, to determine the cutoff age for recommending blepharoptosis evaluation. We also determined the possible association between blepharoptosis and obesity parameters, such as body mass index (BMI) and waist circumference (WC). RESULTS: There was astrong association between older age and the prevalence of blepharoptosis. The cutoff age for recommending blepharoptosis evaluation was 63 years for males, 70 years for females, and 66 years for all patients. Patients with a high BMI and large WC had a higher prevalence of blepharoptosis in all age groups except for those aged over 80 years. The association of blepharoptosis with BMI according to age group showed that in the 50-59 and 60-69 years age groups, blepharoptosis prevalence and BMI were higher. However, in the 70-79 and 80-89 years age groups, extremely obese patients (BMI > 30) showed a decreased blepharoptosis prevalence. CONCLUSIONS: Moderate to severe blepharoptosis can result in poor visual function and exacerbate headaches and depression, leading to decreased quality of life. This study proposed an appropriate age threshold for recommending evaluation of patients with blepharoptosis among the general population of Korea.

Obstructive Lymphangitis Precedes Colitis in Murine Norovirus-Infected Stat1-Deficient Mice.

Murine norovirus (MNV) is an RNA virus that can prove lethal in mice with impaired innate immunity. We found that MNV-4 infection of Stat1-/- mice was not lethal, but produced a 100% penetrant, previously undescribed lymphatic phenotype characterized by chronic-active lymphangitis with hepatitis, splenitis, and chronic cecal and colonic inflammation. Lesion pathogenesis progressed from early ileal enteritis and regional dilated lymphatics to lymphangitis, granulomatous changes in the liver and spleen, and, ultimately, typhlocolitis. Lesion development was neither affected by antibiotics nor reproduced by infection with another enteric RNA virus, rotavirus. MNV-4 infection in Stat1-/- mice decreased expression of vascular endothelial growth factor (Vegf) receptor 3, Vegf-c, and Vegf-d and increased interferon (Ifn)-γ, tumor necrosis factor-α, and inducible nitric oxide synthase. However, anti-IFN-γ and anti-tumor necrosis factor-α antibody treatment did not attenuate the histologic lesions. Studies in Ifnαßγr-/- mice suggested that canonical signaling via interferon receptors did not cause MNV-4-induced disease. Infected Stat1-/- mice had increased STAT3 phosphorylation and expressed many STAT3-regulated genes, consistent with our findings of increased myeloid cell subsets and serum granulocyte colony-stimulating factor, which are also associated with increased STAT3 activity. In conclusion, in Stat1-/- mice, MNV-4 induces lymphatic lesions similar to those seen in Crohn disease as well as hepatitis, splenitis, and typhlocolitis. MNV-4-infected Stat1-/- mice may be a useful model to study mechanistic associations between viral infections, lymphatic dysfunction, and intestinal inflammation in a genetically susceptible host.

Complete Excision of a Simple Dacryops Using Fibrin Sealant and Trypan Blue Mixture.

A 69-year-old woman presented to the oculofacial plastic service with a painless superotemporal subconjunctival mass in the OS. Over the past year, the lesion had been progressively enlarging, resulting in horizontal diplopia with lateral gaze. Visual acuity was within normal limits with no evidence of optic neuropathy. On examination, the lesion was tense, transilluminated, and was clinically consistent with a simple dacryops. Complete excision of the lesion was planned under local anesthesia with monitored care. To facilitate complete removal of the lesion, fibrinogen and a mixture of thrombin and trypan blue were injected to fill the cyst cavity. This blue-stained fibrin clot allowed for easy visualization of the border and ensured complete excision without collateral damage to surrounding normal tissue. Simple dacryops is often difficult to remove completely with its capsule intact and this technique allows for clear delineation of the cyst and preservation of epithelial integrity for complete and efficient removal.

Surgical Feasibility of Curtler-Beard Reconstruction for Large Upper Eyelid Defect.

PURPOSE: To report long-term surgical outcomes of Cutler-Beard reconstructive surgery in patients with large full-thickness upper eyelid defects following malignant tumor excision. METHODS: The medical records of 5 consecutive patients with full-thickness upper eyelid defects following tumor resection who underwent Cutler-Beard surgery were reviewed retrospectively between April 2005 and November 2018. Surgical procedure comprises 2 stages: first, complete tumor resection followed by bridged full-thickness lower eyelid advancement flap; second, separation of the closed eyelid with eyelid margin repair 7 to 9 weeks later. Postoperative anatomical, functional and cosmetic outcomes, and complications were evaluated during follow-up at 22 to 77 months. RESULTS: Patients were in the age group of 49 to 75 years, including 3 (60%) females and 2 (40%) males. Three of the 5 patients (60%) exhibited sebaceous cell carcinoma and 2 (40%) showed squamous cell carcinoma. Three patients (60%) underwent Cutler-Beard surgery after recurrence of primary carcinoma following previous operation. Three patients underwent revision surgery with entropion, 2 underwent correction for wound dehiscence and 1 was treated with symblepharon lysis. No serious or permanent ocular complications were observed during the operation or follow-up with the patients. The procedure resulted in good aesthetic quality and acceptable sequelae at the donor site. CONCLUSIONS: Cutler-Beard procedure for the reconstruction of large and full-thickness upper eyelid defects is an effective procedure with satisfactory long-term results, although a few patients may require minor revision surgery.

Association between pterygium, sun exposure, and serum 25-hydroxyvitamin in a nationally representative sample of Korean adults.

PURPOSE: Ultraviolet-B (UVB) light exposure is the major risk factor for developing a pterygium, and serum 25-hydroxyvitamin D (25(OH)D) level is an objective measure of UVB light exposure. In this study, we investigated the association between pterygium, sun exposure, and serum 25(OH)D. METHODS: This population-based, cross-sectional study comprised 12,258 adults (aged ≥19 years) participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2012. The enrolled subjects underwent interviews, clinical examinations, and laboratory investigations. The serum 25(OH)D levels were measured, and pterygium was examined by using a slit lamp. We used three adjusted logistic regression models and selected covariates as potential confounders. RESULTS: The overall prevalence of pterygium was 7.09, and 53.1% of these subjects were women. The prevalence of pterygium was higher in elderly subjects and those who lived at low latitudes. In multivariate analysis with adjustment for confounding factors, subjects with a serum 25(OH)D level > 30 ng/mL, 25-30 ng/mL, and 15-20 ng/mL had an odds ratio (OR) (95% confidence interval [CI]) of 1.565 (1.035-2.366), 1.545 (1.086-2.198), 1.8 (1.358-2.386), and 1.535 (1.216-1.938), respectively, compared to those with a serum 25(OH)D level < 15 ng/mL. Subjects with a daily sun exposure > 5 h had an OR (95% CI) of 1.761 (1.395-2.223) compared to subjects with a daily sun exposure < 2 h. CONCLUSION: The present study provides epidemiological evidence of an association of daily sun exposure and serum 25(OH)D levels with pterygium in a representative Korean population.

Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions.

All-trans retinoic acid (atRA) is a front-line treatment of acute promyelocytic leukemia (APL). Due to its activity in regulating the cell cycle, it has also been evaluated for the treatment of other cancers. However, the efficacy of atRA has been limited by atRA inducing its own metabolism during therapy, resulting in a decrease of atRA exposure during continuous dosing. Frequent relapse occurs in patients receiving atRA monotherapy. In an attempt to combat therapy resistance, inhibitors of atRA metabolism have been developed. Of these, ketoconazole and liarozole have shown some benefits, but their usage is limited by side effects and low potency toward the cytochrome P450 26A1 isoform (CYP26A1), the main atRA hydroxylase. We determined the pharmacokinetic basis of therapy resistance to atRA and tested whether the complex disposition kinetics of atRA could be predicted in healthy subjects and in cancer patients in the presence and absence of inhibitors of atRA metabolism using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of atRA disposition was developed and verified in healthy individuals and in cancer patients. The population-based PBPK model of atRA disposition incorporated saturable metabolic clearance of atRA, induction of CYP26A1 by atRA, and the absorption and distribution kinetics of atRA. It accurately predicted the changes in atRA exposure after continuous dosing and when coadministered with ketoconazole and liarozole. The developed model will be useful in interpretation of atRA disposition and efficacy, design of novel dosing strategies, and development of next-generation atRA metabolism inhibitors.

A cyclic vertical deviation with dysthyroid ophthalmopathy: a case report.

BACKGROUND: Cyclic strabismus is a very rare condition of ocular motility characterized by alternating strabismus and orthotropia. We report a patient with a 48-h cycle of vertical deviation associated with dysthyroid ophthalmopathy that spontaneously resolved. CASE PRESENTATION: A 40-year-old woman experienced sudden onset vertical double vision. She had already been diagnosed with hyperthyroidism. Asymmetric enlargement of the inferior and medial rectus muscles was demonstrated in her left eye on computed tomography, and was compatible with dysthyroid ophthalmopathy. She clearly described the "every-other-day" pattern of diplopia that spontaneously switched around 8 o'clock every night. She exhibited left hypotropia of 35 prism diopters on a bad day, and 7 prism diopters on a good day. CONCLUSIONS: This case illustrates that cyclic vertical deviation may spontaneously resolve along with the course of the underlying diseases that initiated the cyclic deviation, especially in patients with conditions involving motor component changes such as dysthyroid ophthalmopathy.

Refractive error characteristics in patients with congenital blepharoptosis before and after ptosis repair surgery.

BACKGROUND: We examined the effect of surgical repair on the pattern of refractive errors in Korean patients with congenital blepharoptosis. METHODS: We reviewed the clinical records of 54 patients with congenital blepharoptosis who attended our hospital from 2006 to 2012 and underwent a detailed refractive examination before and after ptosis repair surgery. Among them, 21 of the patients whose refractive data was available for both before and after the surgery were included in order to observe the effect of ptosis repair surgery on refractive error characteristics. The astigmatism groups were divided into three subgroups: with-the-rule (WTR), against-the-rule (ATR), and oblique astigmatism (OA). We also evaluated the severity of astigmatism. RESULTS: Before surgery, the ptotic eyes had more severe astigmatism and a greater percentage of OA than the fellow eyes. The changes in astigmatism magnitude before and after surgery were not significant, but the proportion of subjects with OA increased significantly. In ptotic eyes, amblyopia was found in 14 eyes (20.9 %). 3 eyes (4.5 %) were from solely occlusive visual stimulus deprivation due to severe ptosis, and 11 eyes were from refractive errors. Among refractive errors, amblyogenic astigmatism made up to the largest proportion of patients (8 patients, 11.9 %). CONCLUSIONS: Ptotic eyes had more severe astigmatism and more OA than fellow eyes. Amblyogenic astigmatism was more common in ptotic eyes. A change in astigmatism toward the OA axis was significantly detected after surgery, and that can be possible amblyogenic cause. Therefore, the correction of astigmatism before and after ptosis repair surgery is very important to prevent amblyopia.

Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket.

Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 ±â€Š37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball.

Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.

Knowledge of the regulation of testicular retinoic acid synthesis is crucial for understanding its role in spermatogenesis. Bisdichloroacetyldiamines strongly inhibit spermatogenesis. We reported previously that one of these compounds, WIN 18,446, potently inhibited spermatogenesis in rabbits by inhibiting retinoic acid synthesis. To understand how WIN 18,446 inhibits retinoic acid synthesis, we characterized its effects on human retinal dehydrogenase ALDH1A2 in vitro as well as its effects on retinoid metabolism in vivo using mice. WIN 18,446 strongly and irreversibly inhibited ALDH1A2 in vitro. In vivo, WIN 18,446 treatment completely abolished spermatogenesis after 4 weeks of treatment and modestly reduced adiposity in mice fed a chow diet. Effects of WIN 18,446 on retinoid concentrations were tissue-dependent. Although lung and liver retinyl ester concentrations were lower in WIN 18,446-treated animals, adipose retinyl ester levels were increased following the treatment. Interestingly, animals treated with WIN 18,446 had significantly higher circulating retinol concentrations compared with control mice. The effect on spermatogenesis by WIN 18,446 was not prevented by simultaneous treatment with retinoic acid, whereas effects on other tissues were partially or completely reversed. Cessation of WIN 18,446 treatment for 4 weeks reversed most retinoid-related phenotypes except for inhibition of spermatogenesis. Our data suggest that WIN 18,446 may be a useful model of systemic acquired retinoic acid deficiency. Given the effects observed in our study, inhibition of retinoic acid biosynthesis may have relevance for the treatment of obesity and in the development of novel male contraceptives.

A patient with combined corneal and ingrowing conjunctival tissue tattooing by micropigmentation method.

PURPOSE: This report describes the clinical efficacy of combined corneal and conjunctival micropigment tattooing for the treatment of a corneoconjunctival opacity. CASE SUMMARY: Combined corneal and conjunctival micropigment tattooing was performed on a 39-year-old man who had a cosmetic problem due to traumatic corneoconjunctival opacity. After removal of the corneal epithelium, a 30-gauge needle filled with dye was placed into the corneal stroma. The dye was injected into the stroma and conjunctiva. The patient was followed up for 24 months postoperatively. Although some of the dye dissipated, the majority of it remained in place 24 months after surgery. The patient had no specific postoperative complications and was satisfied with the surgical results. We obtained cosmetically good results. CONCLUSIONS: Combined corneal and conjunctival micropigment tattooing can be an effective treatment for patients with a corneoconjunctival opacity.

Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice.

OBJECTIVES: We examined the return to fertility and transgenerational impact of treatment with WIN 18,446, an experimental male contraceptive, in mice. STUDY DESIGN: We paired male mice treated with WIN 18,446 for 4 weeks to suppress spermatogenesis, followed by a 9-week recovery, and mated them with normal females to assess fertility. F1 generation mice were subsequently mated to ascertain any transgenerational impact of treatment on fertility. Testes were examined histologically. RESULTS: WIN 18,446-treated mice and their progeny produced normally sized litters (6.5 pups per litter after treatment and 7.3 pups per litter from the progeny). However, testes histology revealed rare residual intratesticular foci of mineralization after treatment. CONCLUSIONS: Fertility normalizes after WIN 18,446 treatment, and progeny also have normal fertility.

Current status of contact lenses usage in Korea: A population-based cohort study 2021.

PURPOSE: To investigate trends in contact lens usage in a nationally representative sample of the Korean population in 2021. METHODS: For this retrospective study, we analyzed data of 3,601 Korean participants aged 10-59 years, from the Korea National Health and Nutrition Examination Survey (KNHANES 2021 version), who underwent eye examination, of whom 1,136 individuals (274 men and 862 women) were contact lens users. The demographic trend among Korean contact lens wearers was examined using statistical analyses to investigate the changes in their contact lens-wearing experience, duration of lens use, type of lens used, location of purchase, presence of an Eye Care Practitioner(ECP)'s prescription, lens-related ophthalmic complications, and type of lenses worn at the time of complications, according to sex. Multivariable logistic regression analysis was conducted to examine the association of each variable with the rate of complications and use of soft lenses. RESULTS: The average age of the contact lens users was 33.42±0.33 years, with 70.36% (weighted percentage) of users being women who used contact lenses for significantly longer periods than men (p<0.001). Additionally, only wearing of cosmetic lenses was significantly correlated with the occurrence of complications (p = 0.006), and 6.76% of users purchased lenses without a prescription. Multivariate analysis among the contact lens users revealed a significant relationship between the complication rate and female sex (p = 0.002), pre-existing eye disease diagnosed by ECPs (p = 0.0288), and duration of contact lens use (p<0.0001). CONCLUSION: We identified sex differences in contact lens usage trends in Korea. The main changes observed were an increase in middle-aged lens users and a decrease in female users compared to that in the early 2000s. In addition, contact lens complications were significantly associated with sex and pre-existing eye disease. Therefore, those wearing contact lenses for extended periods should exercise caution and consult eye care specialists in the presence of any symptoms.